EFFICACY OF MEROPENEM IN EXPERIMENTAL MENINGITIS

Meropenem and comparator antibiotics, including ceftriaxone, ceftazidi me, benzyl penicillin and a combination of ampicillin plus gentamicin, were evaluated in a model of bacterial meningitis in the guinea-pig. The model is an acute infection in which challenge with each organism, if untreated, causes an increase in numbers of white blood cells, ele vation of protein concentrations and 6-8 log(10) cfu/mL of bacteria in the CSF. Infections caused by Haemophilus influence, Neisseria mening itidis, three strains of Streptococcus pneumoniae (two penicillin-resi stant), Escherichia coli, Pseudomonas aeruginosa and Listeria monocyto genes all responded to meropenem, which was as active as the comparato r agents in all studies, and was more active in most. Of particular no te were the results seen against S. pneumoniae (penicillin-resistant) infections, in which meropenem was significantly more effective than c eftriaxone. Also notable were results from the P. aeruginosa infection where meropenem, at low doses, was more effective than ceftazidime. A ctivity against L. monocytogenes was equivalent to that produced by tr eatment with the combination of ampicillin plus gentamicin, even when treatment was delayed. These results show that, in an animal model, me ropenem penetrates into CSF in concentrations sufficient to produce si gnificant reductions in the numbers of common and less common pathogen s.